Genetic Variant ZDHHC2:p.Ala10Val (chr8-17156752-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_016353.5(ZDHHC2):c.29C>T(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZDHHC2
NM_016353.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

ZDHHC2 (HGNC:18469): (zinc finger DHHC-type palmitoyltransferase 2) Enables protein homodimerization activity and protein-cysteine S-palmitoyltransferase activity. Involved in several processes, including peptidyl-L-cysteine S-palmitoylation; regulation of protein catabolic process; and regulation of protein localization to plasma membrane. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC2 links:

ENSG00000298219 (HGNC:):

ENSG00000298219 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.119707525).

BP6

Variant 8-17156752-C-T is Benign according to our data. Variant chr8-17156752-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2534764.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016353.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC2	NM_016353.5	MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 13	NP_057437.1	Q9UIJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC2	ENST00000262096.13	TSL:1 MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 13	ENSP00000262096.8	Q9UIJ5
ZDHHC2	ENST00000955296.1		c.29C>T	p.Ala10Val	missense	Exon 1 of 15	ENSP00000625355.1
ZDHHC2	ENST00000955297.1		c.29C>T	p.Ala10Val	missense	Exon 1 of 12	ENSP00000625356.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1348140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664716

African (AFR)

AF:

0.00

AC:

AN:

27408

American (AMR)

AF:

0.00

AC:

AN:

30620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23586

East Asian (EAS)

AF:

0.00

AC:

AN:

29878

South Asian (SAS)

AF:

0.00

AC:

AN:

75106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4836

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1055144

Other (OTH)

AF:

0.00

AC:

AN:

55582

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.41

PhyloP100

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.19

REVEL

Benign

0.26

Sift

Benign

0.26

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.049

MutPred

0.12

Gain of helix (P = 0.062)

MVP

0.27

MPC

0.020

ClinPred

0.14

GERP RS

-1.8

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.026

gMVP

0.27

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over